Microfiltration is known as are filtration cells that produce a filtrate through microfiltration. U.S. Pat. No. 4,818,493 discloses a filtration cell for separating a filtrate from a fluid, such as plasma from blood, by means of microfiltration. U.S. Pat. No. 5,000,923 discloses a particular filtration cell having application in the art of filtering plasma from blood by a microfiltration. U.S. Pat. No. 4,695,430 discloses an automated apparatus for effecting the filtration of biological fluids using a filtration cell of the type disclosed in the aforesaid two patents, and then further processing the cell to analyze the filtrate for various biological aspects, such as blood clotting time.
In recent years, the process of filtering and analyzing the fluid has been further developed to the point where it is full automated. There is, however, a remaining problem; namely the problem of specimen transfer. Present day microfiltration apparatus, such as the apparatus disclosed in the three above-cited patents and improvements thereon, provide a continuous flow operation for obtaining high quality biologic and other samples. Each specimen can be processed in about thirty seconds. Moreover, the capital cost for the equipment is less than alternative equipment for accomplishing the same result. Despite its advantages, such apparatus does not solve all the problems of automation. Current approaches to specimen transfer severely limit automation. Specimen transfer requires precision pumps and rinse solution. All automated specimen processing systems share these problems. This translates into increased equipment costs as well as biohazardous waste transfer and disposal costs. Other costs include operating costs such as reagent fluid, disposable tubing, waste containers and waste transfer and disposal expenses.
Each specimen transfer requires additional time in the process cycle. Specimen transfer takes about 45 seconds to perform using the Bio/Data Corporation MCA 310 which is a present day version of the apparatus disclosed in the three patents cited above. The filtration cycle requires only 17 to 20 seconds. Thus the specimen transfer process, when coupled with the filtration cycle requires about 1 minute. This is a reasonable rate for processing specimens, but the preliminary step of specimen transfer takes almost three quarters of that time. Analysis of the specimen transfer process helps define the problem. The specimen transfer operation may be outlined as follows:
1. Loading the specimen container.
2. Mix specimen
3. Positioning the specimen container at a 30 degree down angle.
4. Indexing the piercing needle up 30 degrees from the horizontal.
5. Driving the needle forward into the specimen tube and pumping out a volume specimen. In the MCA 310, this process occurs in two different sized specimen tubes, however, it would be desirable to carry out this step independent of the size of the specimen tubes.
6. Retracting the needle.
7. Indexing the needle down to a vertical position and then extending the needle into the cell reservoir chamber.
8. Dispensing a volume of specimen into the cell.
9. Retracting the needle.
10. Indexing the needle to a third position.
11. Extending the needle into a rinse chamber and then dispensing a volume of rinse solution greater than the specimen volume.
Moreover, apparatus for performing the transfer operation includes the following:
A rinse solution reservoir.
A precision pump.
A mechanism for mixing the specimen.
A mechanism for articulating the piercing needle.
A waste collection container.
There is a need in the art for a microfiltration cell which minimizes the time associated with specimen transfer and the additional equipment associated therewith and which improves the time associated with use of microfiltration cells. There is also a need in the art for a microfiltration cell which provides further control of specimen and sample handling and the type and volume of samples which may be taken as filtrate from the microfiltration cell. Additionally, there is a need for a microfiltration cell which improves internal specimen handling and removes as much specimen as possible in order to provide either small or large volumes of sample depending on particular applications. The present invention uses a single pressure source and can achieve these advantages such as others as outlined further below in the description of the present invention.
The invention includes a filtration cell capable of direct sampling of a fluid from a container. The filtration cell comprises a reservoir to receive the fluid to be filtered; a filter membrane capable of filtering the fluid to provide a filtrate, the membrane being operatively associated with an opening in the reservoir such that fluid is able to flow over the filter membrane; a base to receive the filtrate after it passes through the membrane, the base including a path through which the filtrate is guided to an outlet from the filtration cell; a piercing instrument supported in the filtration cell adapted to pierce a container holding the fluid to be filtered, the piercing instrument including a hollow interior in open communication with the reservoir and adapted to be in open communication with an interior of a pierced fluid container, and a flow channel extending between the piercing instrument and the reservoir such that the hollow interior of the piercing instrument is in communication with the reservoir through the flow channel, wherein the flow channel is open to the filter membrane so that fluid to be filtered can be directly passed from a fluid container over the filter membrane as it is transferred from the hollow interior of the piercing instrument, through the flow channel and into the reservoir.
A process for directly transferring a specimen of a fluid to be filtered from a fluid container to a filtration cell is included within the invention and comprises (a) providing a filtration cell comprising a reservoir, a filter membrane operatively associated with an opening in the reservoir, a base configured to receive filtrate passing through the membrane, the base including a path through which the filtrate is guided to an outlet from the filtration cell, a piercing instrument adapted to pierce a container holding the fluid to be filtered, the piercing instrument including a hollow interior in fluid communication with both the reservoir and an interior of a pierced container, and a flow channel extending between the piercing instrument and the reservoir, the flow channel being open to the filter membrane; (b) providing a container holding a quantity of fluid to be filtered; (c) piercing the container with the piercing instrument; (d) providing an airtight connection between the reservoir and a source of air; (e) alternately pressurizing the reservoir with air, and then releasing the air pressure from the filtration cell such that the fluid reciprocally flows across the filter membrane; and (f) collecting the filtrate from the membrane.
In one preferred embodiment of the process, the filtration cell further comprises a second reservoir in fluid communication with the flow channel between the reservoir and the piercing instrument, step (d) further comprises providing an airtight connection between the second reservoir and the source of air, and step (e) further comprises alternately (i) blocking the flow of air into the reservoir, pressurizing the second reservoir with air, and venting the reservoir to release the air pressure and (ii) blocking the flow of air to the second reservoir, pressurizing the reservoir with air, and venting the second reservoir such that the fluid to be filtered flows initially from the initially from the container to the reservoir then reciprocally from the reservoir to the second reservoir across the filter membrane.
In a further preferred embodiment of the process, the filtration cell further comprises an air inlet port having a passageway therethrough and adapted to receive air from a pressure source, and the method further comprises pressurizing the container after fluid to be filtered is initially transferred to the reservoir to ensure that a substantial amount of the fluid flows from the container to the reservoir.
The invention also includes a filtration cell capable of direct sampling of a fluid from a container. The filtration cell comprises (a) a first reservoir and a second reservoir to receive the fluid to be filtered; (b) a filter membrane capable of filtering the fluid to provide a filtrate, the membrane being operatively associated with an opening in the first reservoir and an opening in the second reservoir such that fluid is able to flow over the filter membrane; (c) a base to receive the filtrate after it passes through the membrane, the base including a path through which the filtrate is guided to an outlet from the filtration cell; (d) a piercing instrument supported in the filtration cell adapted to pierce a container holding the fluid to be filtered, the piercing instrument including a hollow interior in open communication with the first reservoir and the second reservoir and adapted to be in open communication with an interior of a pierced fluid container; and (e) a flow channel extending between the piercing instrument and the second reservoir and in fluid communication with the first and second reservoirs such that the hollow interior of the piercing instrument is in communication with the first and second reservoirs through the flow channel, wherein the flow channel is open to the filer membrane so that fluid to be filtered can be directly passed from a fluid container over the filter membrane as it is transferred from the hollow interior of the piercing instrument through the flow channel and into the first reservoir and thereafter flow reciprocally from the first reservoir to the second reservoir.
The invention also includes a filtration system capable of direct sampling of a fluid from a container. The filtration system comprises a filtration cell and a filter head in communication with a pressure source and adapted to seal the reservoir of the filtration cell. The filtration cell of the filtration system comprises a reservoir to receive the fluid to be filtered; a filter membrane capable of filtering the fluid to provide a filtrate, the membrane being operatively associated with an opening in the reservoir, a base to receive the filtrate after it passes through the membrane, the base including a path through which filtrate is guided to an outlet from the filtration cell; a piercing instrument supported in the filtration cell adapted to pierce a container holding the fluid to be filtered, the piercing instrument including a hollow interior in open communication with the reservoir and adapted to be in open communication with an interior of a pierced fluid container, and a flow channel extending between the piecing instrument and the reservoir such that the hollow interior of the piercing instrument is in communication with the reservoir through the flow channel, wherein the flow channel is open to the filter membrane so that fluid to be filtered can be directly passed from a fluid container over the filter membrane as it is transferred from the hollow interior of the piercing instrument, through the flow channel and into the reservoir.